HALOPERIDOL REGULATES NEUROTENSIN GENE-EXPRESSION IN STRIATUM OF C-FOS-DEFICIENT MICE

The immediate-early gene c-fos has been proposed to play a role in ind uction of neurotensin/neuromedin N (NT/N) gene expression in the stria tum following acute haloperidol (HAL) treatment. We utilized mice with targeted disruption of the c-fos gene to directly test this hypothesi s. A robust increase in NT/N gene expression was observed in the dorso lateral striatum (DLSt) in both wild-type (WT) and c-fos-deficient mic e 4-6 h after a single injection of HAL (1 or 4 mg/kg) indicating that products of the c-fos gene are not absolutely required for induction of NT/N mRNA. The basal expression of preprotachykinin, preproenkephal in and preprocholecystokinin mRNAs did not differ between WT and c-fos knockout mice. HAL treatment first increased striatal NT/N mRNA on po stnatal day (PD) 10. HAL-induced NT/N mRNA levels were significantly l ower in c-fos knockout mice than in WT mice on PD 10 and 15. These fin dings indicate that reliance on c-fos may be greater earlier in develo pment and that redundant molecular pathways can lead ro induction of N T/N mRNA in mouse striatum. (C) 1997 Elsevier Science B.V.